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Abstract

There are still some controversies on the association between dietary folate intake
and the risk of upper gastrointestinal cancers including esophageal, gastric and pancreatic
cancers. Hence, a comprehensive meta-analysis on all available literatures was performed
to clarify the relationship between dietary folate intake and risks of upper gastrointestinal
cancers. An electric search was performed up to December 12th, 2016 within the PubMed, MEDLINE AND EMBASE databases. Ultimately, a total of 46
studies which evaluated the association between folate intake and risks of upper gastrointestinal
cancers were included. According to the data from included studies, the pooled results
showed significant association between folate intake and esophageal (OR = 0.545, 95%CI
= 0.432-0.658), gastric (OR=0.762, 95%CI=0.648-0.876) and pancreatic (OR=0.731, 95%CI=0.555-0.907)
cancers. Linearity dose-response analysis indicated that with 100μg/day increment
in dietary folate intake, the risk of esophageal, gastric and pancreatic cancers would
decrease by 9%, 1.5% and 6%, respectively. These findings indicated that higher level
of dietary folate intake could help for preventing upper gastrointestinal cancers
including esophageal, gastric and pancreatic cancers.

Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.

Meta-analysis often requires pooling of correlated estimates to compute regression slopes (trends) across different exposure or treatment levels. The authors propose two methods that account for the correlations but require only the summary estimates and marginal data from the studies. These methods provide more efficient estimates of regression slope, more accurate variance estimates, and more valid heterogeneity tests than those previously available. One method also allows estimation of nonlinear trend components, such as quadratic effects. The authors illustrate these methods in a meta-analysis of alcohol use and breast cancer.

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